Pyridine → US10023592, Example 367

HRID 518533Notes

Reaction equation

HRID 518533 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([O:19][C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=2[F:27])=[C:6]([C:8]2[N:13]3[CH:14]=[N:15][CH:16]=[C:12]3[C:11](=[O:17])[N:10]([CH3:18])[CH:9]=2)[CH:7]=1.N1C=CC=CC=1.[CH3:34][S:35](Cl)(=[O:37])=[O:36]>C1COCC1>[F:27][C:21]1[CH:22]=[C:23]([F:26])[CH:24]=[CH:25][C:20]=1[O:19][C:5]1[CH:4]=[CH:3][C:2]([NH:1][S:35]([CH3:34])(=[O:37])=[O:36])=[CH:7][C:6]=1[C:8]1[N:13]2[CH:14]=[N:15][CH:16]=[C:12]2[C:11](=[O:17])[N:10]([CH3:18])[CH:9]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 31297Methanesulfonyl chlorideHCID 1180221575-[5-Amino-2-(2,4-difluorophenoxyl)phenyl]-7-methylimidazo[1,5-a]pyrazin-8-one

Product 1

HCID 118021905US10023592, Example 367Yield 44.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of the title compound from Example 129, Step 2 (140 mg, 0.38 mmol) in THF (20 ml) was added pyridine (152 mg, 1.90 mmol). Then methanesulfonyl chloride (48 mg, 0.46 mmol) was added to the solution at 0° C. The solution was allowed to warm up to room temperature and heated to reflux for overnight. The reaction mixture was concentrated under reduced pressure to yield the crude product that was purified by prep-HPLC to give the title compound (75.26 mg, 44%) as a yellow solid. 1H NMR (CDCl3, 400 MHz) δ 8.60 (s, 1H), 8.15 (s, 1H), 7.50 (d, J=2.8 Hz, 1H), 7.30 (dd, J=8.8, 2.4 Hz, 1H), 7.18 (td, J=8.8, 5.3 Hz, 1H), 7.00-6.88 (m, 2H), 6.83 (s, 1H), 6.78 (d, J=8.8 Hz, 1), 3.60 (s, 3H), 3.03 (s, 3H). LCMS: 447.0 (M+1)+.

Workup

  1. temperatureheated
  2. temperatureto reflux for overnight
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. customto yield the crude product that
  5. customwas purified by prep-HPLC

Sources & evidence

ORD record
ord-9ce85c7efd4c45b486cb249d6a1e5c71
Source dataset
uspto-grants-2015_08
Patent number
US09115114B2

Reaction notes

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